I have previously demonstrated a commitment towards a career as physician-scientist with focus in head and neck oncology. The goal of this application is to study the antitumor mechanism of a novel therapeutic regimen in head and neck cancer. Every year, approximately 40,000 peoples will be diagnosed with squamous cell carcinomas of the head and neck area with the oral cavity being the most commonly affected site. Despite the recent advances in cancer therapy, the overall survival of patients with oral squamous cell carcinoma (OSCC) has remained unchanged in the past 30 years at approximately 50%. The prognosis is worse for those with recurrent or metastatic disease where the overall survival is approximately 6 months. Dual targeting of EGFR and VEGFR has been proposed to be a promising strategy in anticancer therapy. However, there is a tremendous heterogeneity in response of patients to EGFR and VEGFR targeted therapy. The basis for this heterogeneity has yet to be fully characterized and hinders the proper selection of patients for this therapeutic modality. The goal of this study is to comprehensively study the antitumor mechanism of dual EGFR and VEGFR targeting in OSCC. It is our hypothesis that the down-regulation of StatS in both tumor cell and endothelial compartment of OSCC mediates the enhanced antitumor effects of EGFR and VEGFR inhibition compared to the inhibition of either receptor alone. I will utilize novel in vitro and in vivo models of OSCC and angiogenesis to study his hypothesis. The preclinical findings will then be verified by analysis of tumor specimens from clinical trial of EGFR/VEGFR inhibition in patients with OSCC. The impact of this study on public health lies in establishing the basis for identification of important biomarkers of tumor behavior and therapeutic avenues in the treatment of Q.SCC. The process of performing this study will provide me with the necessary skill, coursework, and guidance towards becoming successful, independent investigator as well as furthering the care and treatment of patients with OSCC.